Winckler T
Department of Pharmaceutical Biology, Institute of Pharmacy, University of Jena, Germany.
Pharmazie. 2013 Jul;68(7):467-73.
Almost 25 years ago, Theo Dingermann published the discovery of a new mobile genetic element in the unicellular microbe Dictyostelium discoideum in the journal Science. An interesting property of this new molecular parasite, the Dictyostelium Repetitive Element (DRE), was that all integrations were found approximately 50 base pairs (bp) upstream of transfer RNA (tRNA) genes in the D. discoideum genome, thus implying an active targeting mechanism to avoid the disruption of host cell genes by the retrotransposition process. Since then, the facultative multicellular "social amoeba" D. discoideum has become a popular model for analyzing complex cellular functions such as cell movement, chemotaxis, phagocytosis, and cell differentiation, important areas of biomedical research that are often hard to investigate in cells from "higher organisms" including humans. Therefore, progress in the development of methods to study Dictyostelium biology has also provoked research on transposable elements in this organism. Early work on the DRE element suggested that studying its molecular mechanism of site-specific integration might promote human gene therapy technology through the design of integrating gene transfer vectors with low intrinsic genotoxic potential. In this review article, I will briefly review the original research performed on the DRE transposable element in the Dingermann lab and report on how the emergence of genomics technologies and the development of tools to analyze de novo retrotransposition events in D. discoideum cells will expand our knowledge of DRE biology in the future.
近25年前,西奥·丁格曼在《科学》杂志上发表了在单细胞微生物盘基网柄菌中发现一种新的移动遗传元件的成果。这种新的分子寄生虫——盘基网柄菌重复元件(DRE)——的一个有趣特性是,在盘基网柄菌基因组中,所有整合都发生在转运RNA(tRNA)基因上游约50个碱基对(bp)处,这意味着存在一种活跃的靶向机制,以避免逆转座过程破坏宿主细胞基因。从那时起,兼性多细胞“社会性变形虫”盘基网柄菌就成为分析细胞运动、趋化性、吞噬作用和细胞分化等复杂细胞功能的热门模型,而这些都是生物医学研究的重要领域,在包括人类在内的“高等生物”的细胞中往往很难进行研究。因此,研究盘基网柄菌生物学方法的进展也引发了对该生物体中可移动元件的研究。早期对DRE元件的研究表明,通过设计具有低内在基因毒性潜力的整合基因转移载体来研究其位点特异性整合的分子机制,可能会促进人类基因治疗技术的发展。在这篇综述文章中,我将简要回顾丁格曼实验室对DRE可移动元件进行的原始研究,并报告基因组学技术的出现以及分析盘基网柄菌细胞中从头逆转座事件的工具的开发将如何在未来扩展我们对DRE生物学的认识。